The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.     

p53-Induced inflammation exacerbates cardiac dysfunction during pressure overload

The rates of death and disability caused by severe heart failure are still unacceptably high. There is evidence that the sterile inflammatory response has a critical role in the progression of cardiac remodeling in the failing heart. The p53 signaling pathway has been implicated in heart failure, but the pathological link between p53 and inflammation in the failing heart is largely unknown. Here we demonstrate a critical role of p53-induced inflammation in heart failure. Expression of p53 was increased in cardiac endothelial cells and bone marrow cells in response to pressure overload, leading to up-regulation of intercellular adhesion molecule-1 (ICAM1) expression by endothelial cells and integrin expression by bone marrow cells. Deletion of p53 from endothelial cells or bone marrow cells significantly reduced ICAM1 or integrin expression, respectively, as well as decreasing cardiac inflammation and ameliorating systolic dysfunction during pressure overload. Conversely, overexpression of p53 in bone marrow cells led to an increase of integrin expression and cardiac inflammation that reduced systolic function. Norepinephrine markedly increased p53 expression in endothelial cells and macrophages. Reducing β₂-adrenergic receptor expression in endothelial cells or bone marrow cells attenuated cardiac inflammation and improved systolic dysfunction during pressure overload. These results suggest that activation of the sympathetic nervous system promotes cardiac inflammation by up-regulating ICAM1 and integrin expression via p53 signaling to exacerbate cardiac dysfunction. Inhibition of p53-induced inflammation may be a novel therapeutic strategy for heart failure.